PROJECT SUMMARY Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma in the US, affects ~22,000 people/year and is a significant clinical problem for cancer patient-oriented research in that it is a curable disease, but one with heterogeneous outcomes. Despite >58% of patients being alive and cured at 5 years with modern chemo- immunotherapy, outcomes are significantly worse for patients who are African American (AA), uninsured, or those who have activated B-cell-like (ABC) biological subtype or a high international prognostic index score. Dr. Flowers has described patient outcomes for biological subtypes of DLBCL, identified racial and socioeconomic disparities in DLBCL, and modeled how race/ethnicity, biological, and socioeconomic factors interact to influence DLBCL survival. However, at present there is no unifying, comprehensive prognostic system that incorporates these parameters. To address the current and long-term unmet health needs of the lymphoma patient population, Drs. Flowers and Cerhan established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (U01CA195568), which will support a broad research agenda aimed at identifying novel clinical, epidemiologic, host genetic, tumor, and treatment factors that significantly influence prognosis and survivorship. LEO will: 1) Recruit >12,000 newly diagnosed lymphoma patients (including 1,000 AA and 1,400 Hispanic participants and 3,700 DLBCLs); 2) Build a tissue bank with extracted tumor DNA and RNA, peripheral blood DNA, serum and plasma; 3) Annotate all cases with clinical, epidemiologic, pathology, and treatment data; 4) Prospectively follow patients to ascertain disease progression/relapse, retreatment, second cancers, survival, and patient-reported outcomes; and 5) Facilitate research projects that use this infrastructure. In addition, Dr. Flowers will utilize LEO protocols and the Georgia state SEER registry to construct a population-based cancer disparities cohort study that will: 1) examine the relationships between DLBCL genomics, ABC subtype, race, pattern of presentation, treatment and survival; 2) develop a computer micro-simulation model that incorporates these data into an online prognostic tool for DLBCL as a decision support tool for patients, clinicians, and other investigators. Dr. Flowers will build on his national leadership on the American Society Hematology Committee on Promoting Diversity, American Society Clinical Oncology Health Disparities Committee, and in clinical research mentorship programs for ASH and the Lymphoma Research Foundation and utilize these resources to recruit, train, and develop a cadre of junior faculty, hematology/oncology fellows, housestaff, and medical students in cancer patient-oriented research with a particular focus on developing minority investigators who will lead the field.